Autism is a neurodevelopmental disorder defined by the presence of social deficits, communication abnormalities and ritualistic-repetitive behaviors. Although the importance of hereditary factors is well established, no specific genes responsible for autism or autistic behaviors have been identified. In this project we propose an approach using mouse models and genome-scale gene expression profiling to discover clusters of genes whose expression profiles identify molecular signatures that are highly predictive of the natural variation in social behaviors and cognitive flexibility, behaviors of clear relevance to understanding the autistic phenotype. Our hypothesis is that variation in the social and cognitive behaviors manifested by autistic individuals are at the extreme of normal genetically controlled variation. Furthermore, we hypothesize that the genetic variation underlying a behavioral trait is a manifestation of unique, stable gene expression profiles within specific regions of the brain. This project will lead to the genetic dissection of novel genotypebehavior correlations relevant to autism. We will achieve this goal by: 1) characterizing social and cognitive behavior phenotypes in a diverse panel of mouse inbred strains and genetically engineered models; 2) generating gene expression profiles for specific brain regions thought to control the targeted behaviors; and 3) identifying associations between behavior and gene expression.